CCFold: rapid and accurate prediction of coiled-coil structures and application to modelling intermediate filaments
CCFold: rapid and accurate prediction of coiled-coil structures and application to modelling intermediate filaments
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DOI：
10.1093/bioinformatics/btx551
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发表时间：
2018-01-15
期刊：
影响因子：
5.8
通讯作者：
Strelkov, Sergei V.
中科院分区：
文献类型：
--
作者：
Guzenko, Dmytro;Strelkov, Sergei V.
动机：代表中间细丝(IF)基本构件的蛋白质二聚体的准确分子结构对于了解中间细丝的组装、使其机械性能合理化以及解释与疾病相关的IF突变的影响至关重要。该二聚体包含一个类似于300个残基的长的阿尔法螺旋盘绕线圈，既不能通过直接的实验结构确定，也不能用标准方法建模来评估。结果：本文提出了一种通用的基于线程的算法CCFold，该算法仅从蛋白质序列中产生螺旋线圈模型。该算法基于对实验确定的结构的统计分析，除了最常见的七重重复模式外，还可以处理任何疏水重复模式。我们证明，CCFold在精度方面优于通用计算折叠，同时速度快几个数量级。通过结合CCFold算法和Rosetta折叠，我们为所有IF蛋白质类生成了具有代表性的二聚体模型。
Motivation: Accurate molecular structure of the protein dimer representing the elementary building block of intermediate filaments (IFs) is essential towards the understanding of the filament assembly, rationalizing their mechanical properties and explaining the effect of disease-related IF mutations. The dimer contains a similar to 300-residue long alpha-helical coiled coil which cannot be assessed by either direct experimental structure determination or modelling using standard approaches. At the same time, coiled coils are well-represented in structural databases.Results: Here we present CCFold, a generally applicable threading-based algorithm which produces coiled-coil models from protein sequence only. The algorithm is based on a statistical analysis of experimentally determined structures and can handle any hydrophobic repeat patterns in addition to the most common heptads. We demonstrate that CCFold outperforms general-purpose computational folding in terms of accuracy, while being faster by orders of magnitude. By combining the CCFold algorithm and Rosetta folding we generate representative dimer models for all IF protein classes.